DESCRIPTION (provided by investigator): Much progress has been made in recent years in finding genes for rare mendelian epilepsies. However, the more common forms of epilepsy that shows a clear genetic component, but is also genetically more complex, show no involvement of those identified genes and has proven more difficult to study. We have investigated the genetic basis of Childhood Absence Epilepsy (CAE), a subform of common idiopathic generalized epilepsy (IGE). We have identified areas of linkage to chromosome 5, 8, 12 and 18. Our results suggest that loci on chromosome 18, 12 and 5 contribute to an increase in general seizure susceptibility. For the chromosome 5 loci, we have been able to use clinical criteria to disentangle heterogeneity. In addition, our results suggest that among an individual with an increased seizure susceptibility, a locus on chromosome 8 confers a risk for absence seizures. Therefore, we have identified a paradigm where a small numbers of interacting genes confer risk for generalized seizures and additional gene(s) determine the seizure type. This paradigm can be extended to all idiopathic generalized epilepsies and would be able to explain the close relationship of clinically different but similar IGE syndromes as well as the overlap of these syndromes seen in patients and their families We will further pursue these results by: 1. Narrowing and confirming the identified linkage regions with a combination of: a) Saturation of those regions with additional microsatellites b) LD mapping with SNPs, 2. Identifying disease causing or contributing mutations by sequencing of candidate genes in those regions, [unreadable] 3. Determinining the way these identified mutations might interact, 4. Determinining if genetic heterogeneity can be disentangled by phenotypic factors Understanding the molecular basis of CAE will enhance our understanding, diagnosis, and treatment of CAE and other epilepsies. The impact on Public Health would be enormous because it is estimated that about 2.5 million people in the US alone suffer from epilepsy . [unreadable] [unreadable] [unreadable]